DESCRIPTION: Diisocyanates remain the most frequent cause of occupational asthma (OA) in developed economies. Four years ago the Yale Occupational and Environmental Medicine Program, in conjunction with investigators from UMass, initiated a multi-disciplinary, large scale cross-sectional study of autobody shops in New Haven (the SPRAY study) to address outstanding questions for primary and secondary control of this highly prevalent condition. Ancillary studies were initiated simultaneously in humans and animals to elucidate mechanism. To date we have demonstrated several key associations between patterns of exposure and clinical, physiologic and immunologic parameters, and begun to elucidate the immunology of the disease. However, success has been hampered by inherent limitations of cross-sectional design and evident healthy worker selection pressures in this industry. We propose now to take further scientific advantage of this extraordinary cohort and our relationship with the subjects and shops to: 1. characterize the natural history of isocyanate exposure by following SPRAY subjects over the next 5 years with repeated exposure assessment and measurements of respiratory and immunologic function. 2. address healthy worker effect by supplementing the existing cohort with an inception cohort of new workers hired during the follow-up period. 3. confirm all cases developing new onset asthma by specific inhalation challenge to establish the exposure patterns, pre-clinical physiologic and immunologic features and host factors which confer risk for isocyanate asthma.